Aseptic Bone Necrosis (Osteonecrosis): Clinical Guidelines

List of Abbreviations

AN — avascular necrosis

ANFH — avascular necrosis of the femoral head

BP — Bisphosphonate

PRM physician — physical and rehabilitation medicine physician

DPD — deoxypyridinoline

ICD-10 — International Classification of Diseases, 10th Revision

BMD — bone mineral density

MDT — multidisciplinary rehabilitation team

MRI — magnetic resonance imaging

CT — computed tomography

PT — physical therapy

CTX-s — resorption marker, type 1 collagen degradation product

I.I. — image intensifier

ESWT — Extracorporeal shock wave therapy

HBO — Hyperbaric oxygenation

NSAIDs — non-steroidal anti-inflammatory and antirheumatic drugs (anti-inflammatory and antirheumatic drugs, M01BX Other anti-inflammatory / antirheumatic agents in combination with other agents, M09AX Other drugs for disorders of the musculoskeletal system)

SYSADOA — Symptomatic Slow Acting Drugs for Osteoarthritis ((M01AX Other non-steroidal anti-inflammatory and antirheumatic drugs, M01BX Other anti-inflammatory / antirheumatic agents in combination with other agents, M09AX Other drugs for disorders of the musculoskeletal system))

DMOADs — Disease-Modifying Osteoarthritis Drugs ((M01AX Other non-steroidal anti-inflammatory and antirheumatic drugs, M01BX Other anti-inflammatory / antirheumatic agents in combination with other agents, M09AX Other drugs for disorders of the musculoskeletal system))

TGF-b — transforming growth factor beta

IGF-I — insulin-like growth factor-1

IGF-II — insulin-like growth factor-2

BMI — body mass index

** — medicinal product included in the VLDNL list (Vital and Essential Drugs)

# — medicinal product for medical use used off-label regarding indications, contraindications, routes of administration, and dosages contained in the instructions for medical use

ATOR — Association of Traumatologist-Orthopedists of Russia

MASTO — Medical Association for Osteonecrosis

ARR — Association of Rheumatologists of Russia

ARO — Association of Rheumoorthopedists

Terms and Definitions

Aseptic bone necrosis (osteonecrosis) — a severe multi-etiology disease associated with the death of bone cells in a specific area of bone tissue, accompanied by impaired blood supply, rapidly leading to the development of secondary arthrosis/arthritis of the adjacent joint.

Idiopathic osteonecrosis — avascular bone necrosis occurring without an apparent cause.

Secondary osteonecrosis — avascular bone necrosis occurring against the background of glucocorticoid intake, alcohol abuse, radiation or chemotherapy, autoimmune diseases, coagulopathies, or trauma.

According to the international classification, osteonecrosis is included in the group of diseases of Class XIII, subgroup M87.

Blair arthrodesis — a surgical technique of tibio-calcaneal arthrodesis of the ankle joint used for avascular necrosis or destruction of the talar body, which consists in the resection of the non-viable talar body and fixation of the tibia to the remaining head and neck of the talus, and to the calcaneus, thereby preserving mobility in the talonavicular joint.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Aseptic bone necrosis (osteonecrosis) is a severe multi-etiology disease associated with the death of bone cells in a specific area of bone tissue, accompanied by impaired blood supply, which rapidly leads to secondary arthrosis/arthritis of the adjacent joint [1]. The most frequent localization is the femoral head, with the femoral and tibial condyles ranking second in prevalence, and the humeral head, talus, etc. being less common [2]. Osteochondropathy of the femoral condyles (König's disease) and the femoral head (Legg-Calvé-Perthes disease) is distinguished as a separate nosological form, since this pathology occurs predominantly in childhood and adolescence. In this case, the presence of open growth plates makes the prognosis of the disease more favorable compared to aseptic necrosis in adults [3].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Secondary aseptic necrosis is more common than idiopathic. The causes of secondary aseptic bone necrosis may include glucocorticoid intake, alcohol intoxication, radiation therapy or chemotherapy, various coagulopathies (DIC syndrome, thrombophilia), systemic diseases (SLE, vasculitis), sickle cell anemia, HIV, hyperlipidemia, liver disease and liver failure, diving and other hyperbaric conditions, pregnancy, and trauma, particularly with vascular integrity disruption (femoral neck fracture, traumatic hip dislocation, impression fracture of the femoral and tibial condyles) [4]. Cases associated with Factor V Leiden mutation, prothrombin G20210A mutation, elevated Factor VIII levels (> 150 IU/dL), and Protein S deficiency (< 67 U/dL) have been described. At the same time, no association of the disease with elevated fibrinogen levels (> 4.0 g/L), Protein C deficiency (55 U/dL) [5], or gene polymorphism PPAR gamma, responsible for lipid metabolism and adipocyte proliferation, although this hypothesis remains very interesting, since according to recent data [6], individuals with elevated lipid levels are significantly more likely to have systemic bone loss, which predisposes to the development of ANFH. In patients with ANFH, coagulation and arterial blood supply disorders are often not confirmed by angiography and laboratory tests [7]. The vascular theory of osteonecrosis of the femoral and tibial condyles is even less likely, given the large number of anastomoses between the arteries supplying the epiphyses [8,9]. Up to 40% of all cases of the disease are accounted for by idiopathic osteonecrosis, the cause of which remains unclear. In these cases, a number of authors assign a special role in the development of ANFH to systemic osteoporosis and local enhancement of bone resorption [10,11,12]. The role of calcium-phosphorus metabolism disorders in the occurrence of AN is evidenced by (Matthew R. Lewington et al.) the development of femoral head osteonecrosis against the background of Albright's disease [13]. A number of researchers consider increased bone resorption in the lesion focus as a key moment in the pathogenesis of ANFH [14,15,16]. The association of ANFH with an imbalance between bone formation and resorption, with the latter prevailing, is confirmed by histomorphometry data in experimentally induced aseptic necrosis [16,17]. These abnormalities reduce bone strength, which under load leads to an increase in trabecular microfractures [18], compressing small vessels. As a consequence of the mechanical compression of the vascular bed, venous and subsequently arterial stasis occurs, which is detected by measuring intraosseous pressure and intramedullary venography. Reduced blood flow against the background of elevated bone marrow pressure is characteristic of early stages of AN [19,20]. Cases of ANFH in pregnant and postpartum women [21] are associated with hypercoagulation, and with a decrease in the strength properties of the femoral head due to increased bone resorption resulting from hormonal changes and increased joint load. 

Ischemia of the femoral head due to mechanical disruption of vascular integrity is the cause of traumatic osteonecrosis of the femoral head (ONFH), as proven on a "ligature model" in experiments [22]. Impaired bone metabolism with the accumulation of trabecular microfractures in the subchondral region is considered one of the leading causes of osteonecrosis of the femoral and tibial condyles [23,24,25]. Continued joint loading against this background leads to disease progression, the volume of bone tissue damage increases, and the conditions for its healing turn out to be unfavorable [26,27].

1.3 Epidemiology of the Disease or Condition

According to the English Register, the incidence of osteonecrosis in the UK population between 1989 and 2003 ranged from 1.4 to 3.0 per 100,000 population. Furthermore, the femoral head was affected in 75.9% of cases [28]. In the United States in the early 2000s, the number of patients with osteonecrosis of the femoral head (ONFH) ranged from 300,000 to 600,000 [29]. Meanwhile, the number of newly detected primary cases of osteonecrosis ranged from 10 to 20 thousand per year [30]. In Japan, the incidence rate is 1.9 per 100,000 population [31]. A bilateral process is more frequently noted (70% of cases) [32,33]. In Russia, aseptic necrosis is not singled out in the morbidity structure of the musculoskeletal system of the adult population, although according to calculations and extrapolation of foreign data, 5 to 8 thousand new cases of the disease should be detected annually. In recent years, an increase in the number of cases of aseptic bone necrosis has been noted both in Russia and abroad, and is associated with the consequences of the novel coronavirus infection (COVID-19) [237].

A distinctive feature of aseptic necrosis of the femoral head is that it mainly affects young, able-bodied individuals (mean age 33–45 years, male-to-female ratio 3:1). In the absence of treatment in the early stages, femoral head collapse develops in 80% of patients within 3–4 years, which necessitates arthroplasty [33]. According to Canadian and Australian registries, arthroplasty is performed in more than 50% of cases within the first 3 years after the detection of ONFH. At the same time, aseptic necrosis of the femoral head is a risk factor for early implant instability [34,35]. It has been shown that the outcomes of primary arthroplasty for ONFH are inferior to those for idiopathic coxarthrosis: revisions within 10–15 years reach 40% [36,37].

Aseptic necrosis of the femoral and tibial condyles more frequently affects older patients (mean age 55 years and older, male-to-female ratio is 1:3), and the efficacy of conservative treatment is much higher. However, the problem of arthroplasty in cases of late pathology detection and the lack of conservative therapy is no less relevant for them [38].

1.4 Features of Coding the Disease or Condition

M87.0 — Idiopathic aseptic bone necrosis;

M87.1 — Drug-induced osteonecrosis;

M87.2 — Osteonecrosis due to previous trauma;

M87.3 — Other secondary osteonecrosis;

M87.8 — Other osteonecrosis;

M87.9 — Osteonecrosis, unspecified.

1.5 Classification of the disease or condition

Classification of Aseptic Necrosis (Osteonecrosis)

The ARCO (Association Research Circulation Osseous) classification (Appendix G1), developed by the international bone research association [39] to assess the severity of femoral head osteonecrosis, combines two classifications—Ficat and Arlet (1980) and Steinberg (1979) [40,41]—and includes 4 main stages of the disease [42].

This classification can also be used to assess the staging in other localizations of osteonecrosis.

In cases of localization in the knee joint, the WORMS, MOAKS, and BLOKS classifications can additionally be used [238,239].

1.6 Clinical presentation of the disease or condition

Regardless of the localization of the process (hip, knee, etc.), patients report pain in the joint region, its intensification with active and passive movements and axial loading [43]. Soft tissue edema in the joint area and skin hyperemia are generally absent, and skin temperature in the joint area remains normal or slightly elevated. Unlike osteoarthritis, in aseptic necrosis the severity of the pain syndrome significantly prevails over the clinical status and does not correspond to the severity of radiographic changes. Pain starts suddenly, often against a background of complete well-being. The anamnesis frequently indicates increased joint stress one to two days before the onset of the pain syndrome. The effect of NSAIDs is short-lived or absent. In the late stages of the disease, with impression of the articular surfaces and the development of secondary osteoarthritis, the pain syndrome may be constant, joint mobility is significantly restricted, and flexion and adduction contractures develop.

Features of the Clinical Presentation of Aseptic Necrosis of the Femoral Head

In aseptic necrosis of the femoral head, groin pain is not always clearly localized and tends to radiate to the gluteal region or the knee joint [44]. Pain in the knee joint may mimic the presentation of gonarthrosis; undulating intensification of pain and its occurrence at night are possible [45]. The earliest symptom of ONFH is considered to be a restriction of rotational movements, especially internal rotation (80–85% of cases). This is followed by a restriction of abduction, and lastly, a decrease in flexion. In later stages, pelvic tilt, flexion-adduction contracture (not always) in the joint, thigh muscle atrophy, and flattening of the gluteal muscles on the affected side are detected. As the disease progresses, muscle atrophy increases. Once the pathological process begins on one side, it has a high probability of appearing on the other within a year [46].

This served as the basis for distinguishing an asymptomatic stage of the disease for the contralateral joint (ARCO stage 0) [42]. In bilateral involvement, as a rule, one of the joints is more severely affected, and the main symptoms are associated with it. Meanwhile, the contralateral joint may remain completely asymptomatic for a long time.

Features of the Clinical Presentation of Aseptic Necrosis of the Femoral and Tibial Condyles

A characteristic feature of the initial stages of aseptic necrosis of the femoral and tibial condyles is pain upon palpation directly over the bone, and the absence of pain in the projection of the joint space. Restriction of passive movements in the knee joint is rare, but flexion and extension are generally painful. Joint effusion (synovitis) and patellar ballottement are rarely detected even in cases where a meniscal tear is simultaneously present (according to MRI data) [44].

Features of the Clinical Presentation of Other Localizations of Aseptic Necrosis

The clinical presentation of other localizations of aseptic bone necrosis has no distinct specific features, therefore the diagnosis is established after performing additional examinations.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for Establishing the Diagnosis/Condition

According to ARCO International, a society of physicians and basic scientists studying bone circulation and related diseases [44], the criteria for establishing a diagnosis of osteonecrosis are pain and restriction of joint motion, the presence of characteristic changes according to instrumental research methods (radiography and magnetic resonance imaging [MRI]), as well as the presence of risk factors in the anamnesis (corticosteroid intake, alcohol abuse, history of trauma, etc.).

The diagnosis indicates the localization, the potential cause (if present), and the stage of the disease, which determines the treatment tactics [3]. If the cause of the disease is unknown, "idiopathic osteonecrosis" should be written in the diagnosis.

Example of Diagnosis Formulation in a patient with aseptic necrosis of the femoral head arising without a known cause:

Diagnosis: M87.0 Idiopathic aseptic necrosis of the right femoral head, stage 2 (ARCO).

2.1 Complaints and Anamnesis

In the acute period of the disease, the patient complains of joint pain (VAS scale for its assessment is presented in Appendix G2. Visual Analog Scale for Pain (VAS)), and impaired limb function. A characteristic feature is the acute onset of pain, which often arises against a background of complete well-being.

The medical history should clarify factors that may cause the development of avascular necrosis:

√ history of systemic corticosteroid use;

√ history of alcohol abuse or poisoning, or intoxications with other chemical compounds;

√ history of systemic diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, sickle cell anemia, etc.);

√ history of joint trauma;

√ history of chemotherapy or radiation therapy;

√ history of hypogonadism;

√ history of medications affecting blood coagulation;

√ history of factors affecting overall bone mass loss (family history of osteoporosis, low body weight, smoking, early menopause, amenorrhea, inadequate dietary calcium intake).

2.2 Physical Examination

• To identify clinical signs of osteonecrosis regardless of its location, all patients with suspected osteonecrosis are recommended a physical examination, including palpation of the area, assessment of the limb axis, determination of the range of passive motion of a single joint in one plane, range of active motion of a single joint in one plane, and the presence of contractures or joint blockages [47,240].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

2.3 Laboratory Diagnostics

• Laboratory tests, including a complete blood count (CBC), general routine biochemical blood test including the study of such biochemical parameters as total blood calcium level and/or ionized blood calcium level, inorganic blood phosphorus level, blood alkaline phosphatase activity, blood creatinine level (with GFR calculation), blood parathyroid hormone level, blood 25-OH vitamin D level, coagulogram (exploratory hemostasis screening), as well as markers of bone remodeling (blood osteocalcin level and urinary deoxypyridinoline level), and a urinalysis are recommended for all patients with a newly diagnosed bone osteonecrosis to perform differential diagnosis with other bone and joint diseases and for personalized pharmacological correction of bone remodeling disorders in the osteonecrosis zone [48,221,222,223,224,241,242,243,244,245,246,247,248,249,250].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: performing the aforementioned tests is due to the fact that the metabolic component in osteonecrosis manifests as bone metabolism dysfunction (decreased BMD and osteoporosis), which is an independent risk factor for the development of osteonecrosis of the femoral head [251,252].

In osteonecrosis, the complete blood count and calcium homeostasis parameters show no deviations from the norm. In case of hypercalcemia and hypercalciuria, hyperparathyroid osteodystrophy and oncological pathology must be ruled out; in case of hypocalcemia, osteomalacia; deviations in blood parathyroid hormone levels require ruling out hyper- or hypoparathyroidism of various origins; an increased erythrocyte sedimentation rate or abnormalities in the blood differential require ruling out bone marrow pathology. Assessment of biochemical markers of resorption and bone formation initially and dynamically after 1 year allows for personalized treatment selection for the patient.

• All patients receiving #cholecalciferol**/alphacalcidol** as part of complex therapy are recommended to have their total and/or ionized blood calcium levels dynamically assessed 3 months after the start of therapy to monitor the dosage of the drugs [54,55,222].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

2.4 Instrumental Diagnostics

Radiography

• Patients with suspected osteonecrosis are recommended to undergo standard radiography of the involved joint in a standing position in two projections, which allows for assessing the state of bone tissue, joint space width, and ruling out comorbid pathology, as well as for treatment and treatment monitoring purposes to evaluate dynamics [45,60].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comment: the method is ineffective for detecting early-stage avascular necrosis. On standard radiography, visualization of the pathology is possible only after the appearance of a sclerosis line at the border between healthy bone and the osteonecrosis zone (stage 2 according to ARCO). When the avascular necrosis zone is localized in the subchondral area, stages 3 and 4 manifest as joint surface deformation, the appearance of the crescent sign, or signs of secondary deforming osteoarthritis of the joint (osteophytes, joint space narrowing, destruction of the acetabular joint surface, etc.) [59].

Magnetic resonance imaging of joints (single joint)

• Patients with suspected osteonecrosis presenting with pain and no significant changes on radiographs are recommended to undergo magnetic resonance imaging of the joints (single joint) using a scanner with a magnetic field strength of at least 1.5 Tesla to detect pre-radiological stages (stages I, II according to ARCO) of osteonecrosis [61,62,63,64].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: manifestations of avascular necrosis at various stages according to MRI data are presented in Appendix A3 (table 1). When pain is present in the hip or knee joint, an MRI scan is also performed for the contralateral joint.

• To monitor the effectiveness of prescribed treatment and determine further management tactics, patients with a confirmed diagnosis of osteonecrosis are recommended to undergo MRI of the joints (single joint) 3 months after starting therapy [61,62,253].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Computed tomography of joints (single joint)

• To determine the presence of joint surface impression or when MRI of the joints (single joint) cannot be performed at the time of diagnosis; when planning surgical treatment; or to monitor disease progression dynamically, are recommended computed tomography of the joints (single joint) [67,68].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comment: CT is the best imaging method for subchondral fracture [69]. CT examination is more informative when deciding on the need for surgical treatment, choosing the surgical approach, performing differential diagnosis between early and late stage III, or monitoring the dynamics of avascular necrosis development after surgical treatment [70].

Whole-body bone scintigraphy

• Whole-body bone scintigraphy is recommended for patients with suspected osteonecrosis only when it is necessary to perform a differential diagnosis between osteonecrosis and oncological diseases, and should not be used as a routine diagnostic method [71,254].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comment: with the advancement of magnetic resonance imaging of joints (single joint), scintigraphy has lost its diagnostic significance in detecting early stages of avascular necrosis [72].

Angiography

• Angiography (depending on the location: arteries of the upper or lower extremity, direct or retrograde), under X-ray guidance, is recommended to assess blood flow in the area of osteonecrosis only in patients when planning surgical treatment using a vascularized bone graft, and should not be used as a routine diagnostic method [73].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

X-ray densitometry

• All patients with osteonecrosis are recommended to undergo X-ray densitometry prior to initiating treatment to rule out or confirm decreased BMD or the presence of systemic osteoporosis, which often accompanies osteonecrosis [48,74].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: the presence of concomitant osteoporosis or decreased BMD is one of the causes for the development or unfavorable course of avascular necrosis, the risk of which increases with age [48,57,251,252].

Systemic BMD deficit can influence the tactics and duration of conservative therapy, as well as the prognosis of the disease. Furthermore, when these two conditions coexist, osteoporosis therapy must be continued even after achieving a therapeutic effect in osteonecrosis [75].

2.5 Other Procedures

Not used.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Currently, the expediency of an interdisciplinary approach to the treatment of bone osteonecrosis is generally recognized, since an integral part of the treatment is pharmacotherapy aimed at normalizing impaired bone metabolism, improving blood supply to the affected area, and, if necessary, surgical intervention. Such patients are managed by an orthopedic traumatologist, rheumatologist, and other specialists who treat patients with a high risk of developing bone osteonecrosis against the background of an underlying disease or ongoing therapy [4].

3.1.1 Features of the orthopedic regimen and lower limb joint offloading

• In osteonecrosis, regardless of the localization of the process in the lower extremities, to reduce the risk of articular surface impression, it is recommended to unload the adjacent joint for at least 3 months [78,79,80,81,82].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: in aseptic necrosis of the femoral head and in the area of other joints of the lower extremities, unloading is carried out by walking on crutches. In osteonecrosis of the femoral and tibial condyles, joint unloading is possible in a semi-rigid orthosis with lateral plastic or metal inserts and a cane in the opposite hand, or in a functional orthosis (valgizing or varizing depending on the affected condyle) without additional support. Unloading of the ankle joint is possible in fixing braces with rigid lateral supports and a cane in the hand opposite to the lesion.

3.1.2 Analgesic therapy

• To relieve pain in patients with osteonecrosis at high risk of gastrointestinal pathology, it is recommended to give preference to coxibs; in patients with moderate/high risk of cardiovascular complications, to short-term use of propionic acid derivatives (naproxen (M01AE02), ibuprofen** (M02AA13), celecoxib (M01AH01)), acetic acid derivatives and related compounds (aceclofenac (M01AB16)), oxicams (lornoxicam (M01AC05) and tenoxicam (M01AC02)) [85,225,255].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comment: in the presence of cardiovascular diseases, NSAIDs are used at the minimum effective dose for short periods. A contraindication for prescribing any NSAIDs is a very high risk of cardiovascular complications, or receiving dual/triple anticoagulant therapy.

In patients with femoral head osteonecrosis, the risk of serious adverse cardiovascular and cerebrovascular events is higher than in a comparable population of individuals without osteonecrosis [86].

• Patients with osteonecrosis who have clinically significant risk factors for NSAID-gastropathy and/or enteropathy when using NSAIDs are recommended to be prescribed proton pump inhibitors (A02BC) and/or rebamipide (A02BX14) [256,306].

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

3.1.3 Basic Pathogenetic (Osteotropic) Pharmacotherapy as the Basis of Conservative Treatment

• As basic therapy for osteonecrosis, all patients, from the first days after the detection of the disease and regardless of its localization, are recommended daily oral administration of calcium preparations, other preparations affecting bone structure and mineralization, and Vitamin D and its analogues [87,88].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: the unique role of calcium and vitamin D in ensuring bone tissue structure and regulating intracellular processes during bone formation has been demonstrated in numerous experimental and clinical studies [89].

• As basic therapy for patients with osteonecrosis, as well as with other bone diseases accompanied by systemic or local loss of bone mineral density, for an adequate intake of consumed calcium, from the first days after diagnosis and regardless of its localization, it is recommended to daily take calcium preparations (A12AA) or #Osteogenon 2 tablets 2 times a day for the first 2 months, then 1 tablet 2 times a day, which should be combined with #cholecalciferol** 10–20 mcg per day or alfacalcidol** 0.5–1.0 mcg per day, or to use combined preparations of calcium carbonate + cholecalciferol or alfacalcidol + calcium carbonate [87,93,94,97,104,222,257,258].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: calcium absorption is reduced in achlorhydria, concurrent administration with tetracyclines, bisphosphonates, iron preparations (ATX B03A), systemic corticosteroids (ATX H02A), while thiazides (diuretics) increase renal calcium reabsorption.

An alternative to the preparations may be #osteogenon in which calcium is in the form of hydroxyapatite (calcium 178 mg and phosphorus 82 mg) [91,92].

3.1.4 Antiresorptive therapy

• In bone osteonecrosis at all stages (ARCO, Appendix G1) against the background of basic therapy carried out from the first days after the detection of the disease, as antiresorptive therapy bisphosphonates or #denosumab** 60 mg once every 6 months are recommended throughout the entire treatment period [102,103,104,222,223].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: in the USA, according to the American Association of Hip and Knee Surgeons (AAHKS), the share of bisphosphonates in the treatment of osteonecrosis of the femoral head is 10% [102]. Their administration is aimed at reducing the intensity of resorption both in the osteonecrosis zone and in the surrounding bone tissue [105]. The use of bisphosphonates, by preventing bone loss in the early stages of the disease, can reduce the risk of subchondral bone collapse [106]. Such a possibility of using BPs has been shown in a number of studies. However, due to the lack of indications for their use in aseptic necrosis in the BP package insert, the prescription of this group of drugs in osteonecrosis can be considered off-label from a legal perspective.

In recent years, publications have appeared regarding such complications with the prescription of bisphosphonates as atrial fibrillation, atypical femoral fracture, jaw necrosis, and esophageal cancer [107-110].

However, a clear causal relationship between the described complications and bisphosphonate intake has not been established [111-113].

• #Alendronic acid** orally at a dose of 70 mg per week is recommended to be considered as a possible drug from the bisphosphonate group for patients with aseptic necrosis, especially in cases of difficulties with the use of intravenous forms of bisphosphonates, for the entire treatment period [103,114].

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

Comments: one of the disadvantages of oral bisphosphonates is their low compliance, which is why the use of intravenous forms is considered more promising.

• #Ibandronic acid, with an administration frequency of 3 mg IV bolus once every 3 months, is recommended as a possible drug from the bisphosphonate group for patients with aseptic bone necrosis throughout the entire treatment period, but for at least 1 year [88,222–224].

GCR CLOCE 3Level of recommendation validity C (Level of evidence – 3).

Comments: it has been shown that #ibandronic acid in patients with early stages of aseptic bone necrosis reduces the risk of disease progression by 3 times [88]. The use of #ibandronic acid together with alfacalcidol** yields a better effect than with #cholecalciferol** [116].

• #Zoledronic acid**, considering the administration frequency (IV infusion 5 mg once a year), is recommended to be considered as the most promising drug from the bisphosphonate group for patients with aseptic bone necrosis throughout the entire treatment period [117,118,119].

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

Comments: in addition to direct antiresorptive action, and consequently the reduction of bone tissue edema [117], bisphosphonates possess a significant analgesic effect, which improves the quality of life of patients [118,119].

• #Denosumab** solution for subcutaneous injection at a dose of 60 mg once every 6 months as a drug that reduces bone resorption for the treatment of osteonecrosis is recommended for patients whose possibility of using bisphosphonates is limited due to impaired renal nitrogen-excreting function, as well as in case of ineffectiveness of used bisphosphonates throughout the entire treatment period, but for at least 1 year [222,223].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: #denosumab** has demonstrated efficacy and safety in the treatment of bone marrow edema—the first stage of osteonecrosis [104].

• In the early stages of aseptic necrosis of the femoral head, osteotropic therapy is recommended for at least 1 year from the start of treatment [120].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: bone tissue restoration in the early stages of aseptic necrosis can occur as early as 3–6 months of treatment, however, considering the peculiarity of bone metabolism in aseptic necrosis, to reduce the risk of recurrence, treatment should be continued for at least 1 year.

• In late stages of osteonecrosis (presence of articular surface collapse), osteotropic therapy is recommended in order to delay the need for total hip arthroplasty and increase the survival period of the endoprosthesis [222,259,260].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

3.1.5 Anabolic therapy

• As anabolic therapy in the treatment of osteonecrosis, it is recommended to administer #teriparatide** subcutaneously at a dose of 20 mcg once daily into the thigh or abdominal area throughout the entire treatment period, for at least 3 months and not more than 2 years [122, 222, 223].

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

Comment: #Teriparatide** is an agent capable of stimulating bone formation. Its efficacy in osteonecrosis has been proven in a comparative study with #alendronic acid** [122].

3.1.6 Vascular therapy

• To exert an angioprotective and antiplatelet effect, improve collateral blood flow, inhibit platelet aggregation with increased microcirculation, and reduce the risk of arterial thrombosis in patients with osteonecrosis, it is recommended to prescribe #dipyridamole** orally at a dose of 25 mg 3 times/day for 3 weeks [88, 222, 223].

GPR CLOC 5Grade of Recommendation C (Level of Evidence – 5).

Comment: considering the possible link between idiopathic osteonecrosis and microcirculation disorders, as well as the presence of an increased risk of cardiovascular disease in patients with avascular necrosis of the femoral head [86], #dipyridamole** is prescribed from the first days after diagnosis to inhibit platelet aggregation and provide an angioprotective effect.

• In cases where avascular necrosis of the femoral head is associated with thrombophilia or hypofibrinolysis, to prevent disease progression at ARCO stages 1–2, antithrombotic agents are recommended as part of complex therapy, specifically #enoxaparin sodium** at a dose of 60 mg daily subcutaneously for 12 weeks, or direct oral anticoagulants from the groups of direct thrombin inhibitors (B01AE) and direct factor Xa inhibitors (B01AF) [126, 127, 262].

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

3.1.7 Other non-steroidal anti-inflammatory and antirheumatic drugs

• In patients with osteonecrosis and concomitant secondary osteoarthritis, regardless of the severity of the pain syndrome, it is recommended to prescribe disease-modifying osteoarthritis drugs (DMOADs): chondroitin sulfate and/or glucosamine preparations for effective symptom relief and a structure-modifying effect with long-term use [263–266].

GPR CLOC 1Grade of Recommendation C (Level of Evidence – 1).

Comments: due to changes in the subchondral bone, alterations in the structure of the hyaline cartilage covering the adjacent joint occur as early as the initial stages of avascular necrosis (bone marrow edema) [130, 131, 132].

Previously, medications in this group were referred to as symptomatic slow-acting drugs for osteoarthritis (SYSADOA) or "chondroprotectors," which according to the international ATC drug classification belong to group M01 "Anti-inflammatory and antirheumatic products".

3.1.8 Intra-articular drug administration

• In patients with osteonecrosis and secondary osteoarthritis, it is recommended to administer intra-articular sodium hyaluronate and viscoelastic sterile implants for intra-articular injection based on hyaluronic acid (Synovial fluid substitute***, Bone-cartilage matrix implant***) in a quantity of 1 to 5 injections at intervals of once a week [134, 135, 222, 223, 229–234].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Platelet-rich plasma

• To improve the outcomes of bone osteonecrosis treatment in combination with other interventions, it is recommended to use platelet-rich plasma in the amount of 4 injections at 7-day intervals [136, 267].

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

• In osteonecrosis, intra-articular administration of glucocorticoids is not recommended for pain relief due to the high risk of disease progression [138].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

3.1.9 Physiotherapy

Pulsed low-frequency electromagnetic field therapy

• Pulsed low-frequency electromagnetic field therapy is recommended as part of the complex treatment of osteonecrosis [139, 140].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: physiotherapeutic treatment (physical therapist examination (consultation)) in some cases allows for a reduction in disease symptoms [139, 140]. Pulsed low-frequency electromagnetic field therapy has a favorable effect on the early stage of osteonecrosis through the stimulation of osteogenesis and angiogenesis, similar to extracorporeal shock wave therapy (ESWT) [141].

Hyperbaric oxygen therapy

• Hyperbaric oxygen therapy is recommended only as part of the complex treatment of osteonecrosis and exclusively in the early stages of the disease [142, 143].

GCR CLOCE 3Level of recommendation validity C (Level of evidence – 3).

Comment: the method is based on increasing tissue oxygenation and improving microcirculation. The reduction of intraosseous edema helps decrease pain and improve the patient's general well-being) [142, 143].

Ozone therapy

• In patients with osteonecrosis with secondary osteoarthritis and preserved articular surface, intra-articular ozone therapy is recommended to reduce local synovial membrane inflammation, improve tissue trophism, and decrease pain [144, 226].

GPR CLOC 2Grade of Recommendation C (Level of Evidence – 2).

Comment: for intra-articular administration, an ozone concentration of 10 to 20 mcg/ml is used, the injection volume ranges from 10 to 40 ml, frequency is 2–3 times a week, the number of injections per course is 5, with 1–2 courses performed annually [307, 308].

The use of ozone therapy is appropriate in the initial stages of osteonecrosis, provided the hyaline cartilage articular surface remains intact. The use of medical ozone is based on its ability to rapidly relieve pain and improve joint mobility. The spread of the method was also facilitated by the absence of side effects associated with ozone [145, 146]. The formation of reactive oxygen species (ROS) and lipid peroxidation (LPO) products [147–149] enhances blood supply [145] and, consequently, improves the trophism of, among other things, the subchondral bone, alterations in which are observed in osteonecrosis. This occurs due to the contact of the vascular endothelium with traces of lipid peroxidation (LPO) products and a significant increase in the amount of nitric oxide (NO), which has a vasodilating effect [150, 151]. Ozone additionally blocks the phosphodiesterase enzyme, which enhances the vasodilating effect of nitric oxide (NO) [152]. According to available data [153, 154], in some cases, the combination of ozone therapy with sodium hyaluronate or platelet-rich plasma (plasmodynamic effect) increases the therapeutic efficacy.

Alternative techniques

• In patients with osteonecrosis who continue to experience pain despite the aforementioned complex therapy, it is recommended to perform prolonged epidural analgesia by administering the local anesthetic #ropivacaine** 0.2% at 4 ml per hour, with a daily administration duration of 8–10 hours for 6–8 days [158].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: the method is intended for early stages of avascular necrosis of the femoral head (before cartilage layer collapse). Medicinal sympathectomy causes a decrease in vascular wall tone, leading to vasodilation, which helps improve microcirculation in the hip joint area. Disease remission lasts up to 12 months. The annual use of the proposed treatment method has made it possible to postpone hip arthroplasty for up to 6 years [158].

3.2 Surgical Treatment

3.2.1 Features of surgical treatment of avascular necrosis of the femoral head

• All patients with avascular necrosis of the femoral head are recommended to have the disease stage, the presence of an impression fracture, and patient age taken into account when choosing the surgical treatment method [29].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

• At stages 1 and 2 of osteonecrosis (ARCO, Appendix G1), to reduce pain and improve blood supply, tunneling (decompression) of the affected area of the femoral head (revascularizing osteoperforation) is recommended, which is performed after previously prescribed conservative therapy [159, 160].

GPR CLOC 3Grade of Recommendation C (Level of Evidence – 3).

Comment: during tunneling, channels are created from the subtrochanteric region through the neck to the affected segment of the head. The effect of the intervention is explained by an increase in local blood supply in the osteonecrosis area and the relief of elevated intraosseous pressure. This surgery is usually used in the early stages of avascular necrosis of the femoral head [161].

Tunneling is performed under the guidance of an image intensifier (fluoroscopy), with images taken in 2 projections. At the same time, it is important to drill the channel up to the osteonecrosis focus without traumatizing the hyaline cartilage covering the focus. Comparison of various osteoperforation techniques revealed no advantages of any single one over the others [162].

• To enhance the effect of core decompression of the aseptic necrosis lesion (orthopedic bone wire***) in patients with stage 1 and 2 osteonecrosis, it is recommended to combine it not only with previously prescribed conservative therapy, but also with intraosseous administration of biological substances (platelet-rich plasma, adipose-derived stromal vascular fraction, bone marrow aspirate concentrate with stimulating effects) [163].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comment: lesion decompression can be combined with the implantation of concentrated bone marrow aspirate, platelet-rich plasma, bone marrow stromal cells (autologous bone marrow cell implantation), etc. [164,165].

Postponing joint arthroplasty for 5 to 10 years in patients who started treatment before femoral head collapse is 94 %, while in collapse at stages 3 and 4 – in 43 % of cases, which the patient should be informed about [166,167].

• At stages 1 and 2 of osteonecrosis (ARCO, Appendix G1) in young patients, to offload the affected area, it is recommended to perform bone reconstruction, bone osteotomy (followed by internal fixation with an orthopedic internal fixation system using plates/screws, non-absorbable, sterile***, universal implantation kit for internal orthopedic fixation system***), which can be performed only in a specialized facility by highly qualified specialists [168,169].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

• At early stage 3 of osteonecrosis (ARCO, Appendix G1), it is recommended to use a vascularized bone autograft, which can be performed only in a specialized facility by highly qualified specialists (Hip arthroplasty, Synthetic bone matrix implant***, Animal-derived absorbable bone matrix implant***, Orthopedic bone wire***) [173,174].

BMR BLEL 3Level of recommendation validity B (level of evidence – 3).

• At late stage 3 of osteonecrosis (ARCO, Appendix G1), it is recommended to perform orthopedic hip replacement or to use (in young patients) a vascularized bone autograft, which can be performed only in a specialized facility by highly qualified specialists: Coated, modular femoral hip prosthesis component***, Ceramic hip prosthesis acetabular component***, Hip prosthesis acetabular component made of combined material***, Polyethylene hip prosthesis acetabular component***, Metal hip prosthesis acetabular component***, Bone cement containing medicinal products***, Bone cement not containing medicinal products***) [174].

BMR BLEL 3Level of recommendation validity B (level of evidence – 3).

Comments: the use of a vascularized bone autograft remains relevant only for a limited number of orthopedic traumatologists skilled in this technique [173,175].

• At stage 4 of osteonecrosis (ARCO, Appendix G1), after subchondral bone collapse and in the presence of pain syndrome, it is recommended to perform orthopedic hip replacement (Total hip replacement, Orthopedic hip replacement (proximal femur resection). Coated, modular femoral hip prosthesis component***, Ceramic hip prosthesis acetabular component***, Hip prosthesis acetabular component made of combined material***, Polyethylene hip prosthesis acetabular component***, Metal hip prosthesis acetabular component***, Total hip prosthesis with metal-on-polyethylene bearing couple***, Total hip prosthesis with metal-on-metal bearing couple***, Total hip prosthesis with ceramic-on-ceramic bearing couple***, Total hip prosthesis with ceramic-on-polyethylene bearing couple***, Total hip prosthesis with ceramic-on-metal bearing couple***, Bone cement not containing medicinal products***, Bone cement containing medicinal products***) [36,166].

GPR CLOC 3Grade of Recommendation C (Level of Evidence – 3).

Comment: according to statistics, from 5 to 17 % of orthopedic hip replacement surgeries are performed for bone aseptic necrosis [28].

• When performing orthopedic hip replacement for bone aseptic necrosis, it is recommended to administer conservative therapy in the preoperative period aimed at correcting impaired bone remodeling to reduce the risk of component migration (increasing prosthesis survivorship) [36,37,121].

GPR CLOC 3Grade of Recommendation C (Level of Evidence – 3).

Comment: the lifespan of prostheses in patients with aseptic necrosis is lower than in arthroplasty for post-traumatic changes or joint osteoarthritis [36,37], which is primarily due to the predominance of bone resorption in this group of patients [16].

In 70 % of cases, aseptic necrosis of the femoral head involves the contralateral joint, which confirms the need to prescribe conservative treatment for 3–6 months prior to surgery to prevent disease progression on the opposite side [121].

• In young patients with aseptic necrosis of the femoral head, due to the high risk of revision surgeries, it is not recommended to use cemented hip prostheses [179].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

• In young patients with aseptic necrosis of the femoral head, it is recommended to use short prosthesis stems (to preserve a greater bone stock for subsequent interventions) and modern bearing couples: ceramic/ceramic, ceramic/cross-linked polyethylene to reduce wear debris generation (Coated, modular femur prosthesis stem***, Coated, modular femoral hip prosthesis component***, Polyethylene hip prosthesis acetabular component***, Ceramic insert for hip prosthesis acetabular component***, Ceramic femoral head prosthesis***, Total hip prosthesis with ceramic-on-ceramic bearing couple***, Total hip prosthesis with ceramic-on-polyethylene bearing couple***, Bipolar femoral head prosthesis component***, Constraining polyethylene insert for hip prosthesis acetabular component***, Hip prosthesis acetabular component made of combined material***, Ceramic hip prosthesis acetabular component***, Bone cement not containing medicinal products***, Bone cement containing medicinal products***) [180,181].

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

Comments: considering that aseptic necrosis is often observed in young or working-age individuals [33], with an average prosthesis lifespan of 10–15 years and initially poor bone quality in this pathology, the use of designs capable of greater bone conservation and modern bearing couples with a low risk of wear will extend the prosthesis lifespan and preserve bone stock for subsequent surgeries [179,180,181].

• In patients with femoral head aseptic necrosis, it is not recommended to use surface replacement arthroplasty (Resurfacing) as an alternative to orthopedic hip replacement due to the high risk of component instability [222,235,236].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: in surface replacement arthroplasty, the femoral head is not completely removed, but only resected to accommodate the femoral component, which is "capped" over it. The method was specifically designed for young patients, but its use in aseptic necrosis is controversial since the load will be fully transmitted to the affected bone tissue of the head. Nevertheless, some authors find no functional differences in young patients after resurfacing compared to orthopedic hip replacement [184]. However, the average follow-up period is only 5.4 years [185].

3.2.2 Features of surgical treatment of aseptic necrosis of the femoral and tibial condyles

• In stages 1–2 osteonecrosis (ARCO, Appendix G1), if severe pain persists 1 month after starting conservative therapy and joint unloading to reduce pain and improve blood supply, core decompression (revascularizing osteoperforation) of the lesion in the femoral or tibial condyle is recommended via an extra-articular approach [186].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: in the early stages of osteonecrosis of the femoral and tibial condyles, the hyaline cartilage structure is completely preserved; therefore, joint unloading and osteotropic therapy can lead to complete joint recovery. However, in some cases, pain may persist due to increased intraosseous pressure [186, 187]. In such cases, to relieve elevated intraosseous pressure, core decompression (revascularizing osteoperforation) of the osteonecrosis lesion is indicated via extra-articular approaches through the femoral or tibial condyle under fluoroscopic guidance.

• In stages 1–2 osteonecrosis (ARCO, Appendix G1) of the tibial or femoral condyles, to enhance the effect of core decompression of the avascular necrosis lesion (revascularizing osteoperforation, orthopedic bone wire***), the administration of stimulating materials or biological products (platelet-rich plasma, bone marrow aspirate concentrate, or multipotent stromal cells) is recommended [188, 189].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: the use of technologies and drugs to stimulate local osteogenesis is currently under active investigation. This is especially true for biological therapy, such as platelet-rich autologous plasma or multipotent stromal cells harvested from bone marrow or adipose tissue [188].

• In stages 1–2 osteonecrosis (ARCO, Appendix G1), diagnostic knee arthroscopy is recommended only in the presence of a loose intra-articular body or joint locking in flexion or extension [190].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: there is evidence that arthroscopy may exacerbate the disease course [191, 192].

• In patients with avascular necrosis and clinical manifestations of intra-articular structural damage (ligaments, menisci), diagnostic arthroscopy is recommended no earlier than 3 months after the initiation of conservative treatment for avascular necrosis [191].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comment: osteonecrosis of the femoral and tibial condyles is often combined with various intra-articular pathologies (partial anterior cruciate ligament injury, meniscal tears or degenerative changes); the question always arises as to what extent the patient's pain is caused by osteonecrosis versus intra-articular changes. Given that diagnostic knee arthroscopy as an isolated procedure can itself cause bone osteonecrosis [190] or worsen pre-existing osteonecrosis, indications for this surgery should be conservative, performed with great caution, and only against the background of ongoing conservative therapy for osteonecrosis [193].

• In stages 3–4 osteonecrosis (ARCO, Appendix G1), core decompression (revascularizing osteoperforation) of the osteonecrotic area is not recommended due to the inefficiency of this procedure [187].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: in late stages of osteonecrosis of the femoral and tibial condyles, osteoperforation is ineffective [187] and in some cases may increase pain due to the spread of bone damage to a greater depth.

• In stages 3–4 osteonecrosis (ARCO, Appendix G1) with a preserved contralateral condyle, in patients under 55 years of age, to reduce load on the damaged joint segment and delay knee arthroplasty, bone reconstruction via tibial corrective osteotomy (Orthopedic bone wire***, Non-absorbable sterile orthopedic bone screw***, Non-absorbable sterile bone fracture fixation plate***, Non-absorbable sterile bone fracture plate fixation set***, Non-absorbable sterile internal orthopedic fixation system using plates/screws***, Synthetic bone matrix implant***, Resorbable animal-derived bone matrix implant***) is recommended [195].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: bone reconstruction via femoral or tibial corrective osteotomy should be performed only after assessing limb alignment, integrity of the contralateral condyle, and diagnostic arthroscopy to confirm healthy hyaline cartilage on the contralateral condyle [105].

• In stages 3–4 osteonecrosis (ARCO, Appendix G1) with a preserved contralateral condyle, in patients under 50 years of age, arthroscopic mosaicplasty of the knee is recommended, but only after conservative treatment, reduction of bone resorption, and bone edema around the osteonecrosis zone [196, 197].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: persistent high-intensity bone resorption is an unfavorable background for performing arthroscopic mosaicplasty of the knee, which can lead to unsatisfactory results with graft resorption. Due to this possibility, osteotropic therapy with bisphosphonates must be administered prior to surgery, and the surgical intervention is performed only after the intensity of resorption (bone resorption markers) and bone edema (control MRI of the joints [single joint]) have decreased [191].

• In case of excessive varus or valgus limb malalignment in patients with avascular necrosis of the condyles forming the knee joint, combining arthroscopic mosaicplasty of the knee with bone reconstruction via femoral and/or tibial corrective osteotomy (Orthopedic bone wire***, Non-absorbable sterile orthopedic bone screw***, Non-absorbable sterile bone fracture fixation plate***, Non-absorbable sterile bone fracture plate fixation set***, Non-absorbable sterile internal orthopedic fixation system using plates/screws***, Synthetic bone matrix implant***, Resorbable animal-derived bone matrix implant***) is recommended to unload the avascular necrosis area [198].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comment: persistence of excessive load on the avascular necrosis zone is an unfavorable factor for arthroscopic mosaicplasty of the knee, which can be one of the causes of unfavorable surgical outcomes. In such cases, limb alignment correction can improve surgical outcomes by reducing the load on the osteonecrosis zone [197].

• In stages 3–4 femoral osteonecrosis (ARCO, Appendix G1) with small or medium condylar defects and a preserved contralateral condyle, unicompartmental knee arthroplasty (Total knee prosthesis with cruciate ligament preservation***, Total knee prosthesis with mobile bearing***, Two-component knee prosthesis***, Coated femoral knee prosthesis component***, Uncoated femoral knee prosthesis component***, Coated tibial knee prosthesis component***, Uncoated polyethylene tibial knee prosthesis component***, Uncoated metallic tibial knee prosthesis component***, Uncoated tibial knee prosthesis component with insert***, Bone cement containing medicinal products***, Bone cement not containing medicinal products***) is recommended only in cases of primary osteonecrosis and in the absence of systemic diseases, limb malalignment, and ligamentous insufficiency [199, 200].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comment: unicompartmental knee arthroplasty for osteonecrosis of the medial femoral condyle (stages 3 and 4) is effective with small (0–10 cm³) and medium (10–20 cm³) lesion volumes according to joint magnetic resonance imaging (single joint) [199].

• In stage 3–4 osteonecrosis (ARCO, Appendix G1) with large lesion volumes (> 20 cm³) and a defect size greater than 50% of the condyle width, orthopedic knee arthroplasty is recommended (Total knee replacement – Cruciate-retaining total knee prosthesis***, Mobile-bearing total knee prosthesis***, Two-piece knee prosthesis***, Coated femoral knee prosthesis component***, Uncoated femoral knee prosthesis component***, Coated tibial knee prosthesis component***, Uncoated polyethylene tibial knee prosthesis component***, Uncoated metallic tibial knee prosthesis component***, Uncoated tibial knee prosthesis component with insert***, Drug-containing bone cement***, Bone cement without medicinal products***) [201].

GPR CLOC 3Grade of Recommendation C (Level of Evidence – 3).

Comment: the growing popularity of unicompartmental knee arthroplasties recently has led to performing this surgery in younger patients with damage to only one compartment of the knee joint. However, in the presence of severe bone defects, the use of such implants carries a high risk of component instability; therefore, total knee arthroplasty should be preferred [201].

3.2.3 Features of surgical treatment of avascular necrosis of the talus

• In stage 1–2 osteonecrosis (ARCO, Appendix G1) of the talus, core decompression (tunneling, revascularizing osteoperforation) of the lesion is recommended if pain persists, no earlier than 3 months after the initiation of conservative treatment [202].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: in patients with stage 1–2 talar osteonecrosis, a pronounced clinical effect of decompression has been proven. However, this procedure is indicated in the absence of positive clinical changes following conservative therapy administered for at least 3 months prior to surgery [202].

The procedure is performed minimally invasively under X-ray (fluoroscopic) guidance [203]. Talar decompression can be combined with the intraosseous administration of biological materials that stimulate remodeling processes [204].

• In stage 3 osteonecrosis (ARCO, Appendix G1) of the talus, bone grafting (osteoplasty, bone reconstruction) of the osteonecrosis lesion combined with previously prescribed conservative therapy is recommended [205].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: grafting (osteoplasty, bone reconstruction) can be performed using either a vascularized autograft on a vascular pedicle from the femoral condyle or the cuboid bone of the foot, or a non-vascularized autograft from the iliac crest or calcaneus. The main objective of grafting is to maintain the talar architecture. The use of a vascularized graft may increase blood flow volume in the area of avascular necrosis [205].

• In stage 3–4 osteonecrosis (ARCO, Appendix G1) of the talus with talar collapse and severe degenerative changes of the ankle joint accompanied by valgus or varus deformity of more than 15 degrees, ankle arthrodesis (foot and ankle arthrodesis) is recommended; in case of complete talar lysis, tibiocalcaneal arthrodesis is performed (Foot and ankle arthrodesis, Foot and ankle arthrodesis using computer modeling, Arthroscopic ankle arthrodesis, Arthrodesis of other joints), or Blair arthrodesis (Orthopedic non-absorbable bone rod***, Orthopedic bone wire***, Orthopedic non-absorbable sterile bone screw***, Orthopedic non-absorbable non-sterile bone screw***, Sterile non-absorbable bone fracture fixation plate with screws***, Non-sterile non-absorbable bone fracture fixation plate with screws***, Sterile non-absorbable bone fracture fixation kit***, Sterile non-absorbable internal orthopedic fixation system using plates/screws***, Synthetic bone matrix implant***, Absorbable animal-derived bone matrix implant***, Drug-containing bone cement***, Bone cement without medicinal products***) [207].

BMR BLEL 3Level of recommendation validity B (level of evidence – 3).

Comments: the advantage of ankle and foot arthrodesis is the ability to correct significant angular deformities at the ankle level [207, 208].

• In stage 3–4 osteonecrosis (ARCO, Appendix G1) of the talus with secondary ankle arthritis, total ankle arthroplasty / orthopedic ankle arthroplasty is recommended (Uncoated tibial ankle prosthesis component***, Uncoated talar ankle prosthesis component***, Fixed-bearing total ankle prosthesis***, Drug-containing bone cement***, Bone cement without medicinal products***, Orthopedic cement insert***) [209].

BMR BLEL 3Level of recommendation validity B (level of evidence – 3).

Comments: this is one of the treatment methods for secondary degenerative changes of the ankle joint [209]. However, the surgery can be performed only if the normal architecture of the talus is preserved. Otherwise, the revision rate due to component instability increases significantly [210]. Currently, there are several generations of ankle prostheses aimed at achieving maximum stability and the possibility of revision interventions.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Medical rehabilitation is recommended for all patients, regardless of the location and treatment method of avascular necrosis (osteonecrosis), as prescribed by a physical and rehabilitation medicine (PRM) physician, physical therapy (PT) physician, or physical therapist (physiotherapist) [141, 212, 221, 223, 269, 274, 277, 299, 304, 305].

GCR BLEL 1Grade of Recommendation B (Level of Evidence – 1).

Comments: rehabilitation protocols depend on the ARCO stage and the chosen treatment strategy (conservative or surgical). Rehabilitation is as effective as decompression and physical therapy in improving joint function and delaying surgical intervention. There is evidence that structured rehabilitation programs alleviate symptoms and slow disease progression in early stages [269, 274, 277, 299].

Comments: up to 3 months, strict unloading of the affected area is necessary along with creating conditions for revascularization and bone tissue repair. In the 2nd stage (up to 6 months), gradual adaptation to axial loading, normalization of movement biomechanics, and preparation for full weight-bearing are required.

In the 3rd stage, from the 6th month onwards, daily motor activity and professional work must be fully restored.

These data substantiate the need for long-term staged rehabilitation to enhance the effectiveness of rehabilitation in patients with osteonecrosis [287, 288, 298, 300].

Comments: in case of lower limb joint involvement, an inpatient rehabilitation stage is advisable; when osteonecrosis is localized in upper limb joints, the rehabilitation stage is determined by the PRM/PT physician depending on the patient's age, general physical condition, and place of residence.

exercise therapy for joint diseases [273,274,275,276,296],

GPR CLOC 2Grade of Recommendation C (Level of Evidence – 2).

hydrokinesiotherapy for joint diseases and injuries, therapeutic underwater jet massage, therapeutic whirlpool baths, therapeutic exercise in a swimming pool, therapeutic swimming in a pool, therapeutic mechanotherapy in water) [274,275,295],

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

manual massage of the joint area and extremity [280],

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

physiotherapy methods – local cryotherapy [296,297],

GPR CLOC 3Grade of Recommendation C (Level of Evidence – 3).

magnetic field therapy, high-intensity pulsed magnetic field therapy [271,272,273,286],

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

low-level laser therapy [279,281],

interferential current therapy, transcutaneous electrical nerve stimulation (TENS) [140,285,288],

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

extracorporeal shock wave therapy (ESWT) [155,156,157,274,275,285,286,288,289,290].

BMR BLEL 3Level of recommendation validity B (level of evidence – 3).

Comments: there are few meta-analyses and systematic reviews in modern databases dedicated exclusively to physical exercises, massage, or classical physiotherapy in the treatment of osteonecrosis.

Nevertheless, there are several high-level-of-evidence key studies that either directly address these methods in osteonecrosis or provide valuable indirect information, for example, on the efficacy of treating other joint diseases, or the physiological mechanisms of action of individual therapeutic factors and their impact on revascularization and blood flow restoration, which is pathogenetically substantiated in the rehabilitation of patients with osteonecrosis [275,276,286,292,302].

Comments: no direct studies investigating the necessity and optimal frequency of repeated rehabilitation courses after a 3-month period of strict unloading were found in available search results. However, there are indirect data and clinical reasoning supporting the need for repeated rehabilitation courses. It has been proven that prolonged regular exposure consolidates and improves achieved results and adapts the joint to the loads of daily and professional activities [275,282,300].

Therefore, after 3 months, the stage of functional adaptation and return to normal loads is carried out. At this stage, exercise therapy, physiotherapy, and mechanotherapy play a key role in restoring muscle strength and endurance [276,278,298,300], which prevents symptom recurrence upon returning to habitual physical activity and work [277,278,282].

The duration of a single course is 10–15 procedures with intervals between courses of at least 3–4 weeks, which is due to the necessity of preventing tissue adaptation to the exposure [282,283,296,301].

hydrokinesiotherapy for joint diseases and injuries, therapeutic underwater jet massage, therapeutic whirlpool baths, therapeutic exercise in a swimming pool, therapeutic swimming in a pool, therapeutic mechanotherapy in water [274,275,294,295],

GCR BLOCE 2Level of recommendation validity B (Level of evidence – 2).

manual massage of the joint area and extremity [280,283,298],

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

biofeedback (BFB) training [314-316],

GR BLEL 3Grade of Recommendation B (Level of Evidence – 3).

correction of impaired gait pattern [324], low-frequency pulsed electromagnetic field therapy [139,140], magnetic field therapy, high-intensity pulsed magnetic field therapy [271,272,273,286],

low-level laser therapy [279],

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

extracorporeal shock wave therapy (ESWT) [155,156,157,274,275,285,286,289,290,291].

GR BLEL 3Grade of Recommendation B (Level of Evidence – 3).

Comments: rehabilitation of patients with osteonecrosis should be psychologically oriented. This is due to the high level of anxiety, pain catastrophizing, and central nervous system sensitization in this disease. Consultation with a psychotherapist or clinical psychologist helps break the vicious cycle of "pain – stress – muscle spasm – increased pain" and improves patient adherence to long-term treatment.

• Ergoterapia is recommended at all stages of osteonecrosis rehabilitation to restore activities of daily living skills, teach safe and energy-saving ways of performing household activities, select mobility assistive devices, and adapt to the environment. Occupational therapy helps maintain the patient's quality of life and social activity during periods of limb function restriction [320-323].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments: occupational therapy aims at "restoring, developing, or compensating for activities of daily living skills that were lost or impaired due to surgery or illness" regardless of their cause. While exercise therapy and physiotherapy aim to restore physiological functions (strength, range of motion, blood circulation), occupational therapy translates these restored functions into actual daily activity – training in eating, dressing, and moving around in domestic conditions.

• Following joint arthroplasty, osteotomy followed by osteosynthesis, or joint arthrodesis, it is recommended to undergo inpatient and outpatient / day hospital rehabilitation according to relevant postoperative programs [279,293,295,296,325].

GPR CLOC 4Grade of Recommendation C (Level of Evidence – 4).

Comments: rehabilitation is carried out by the MDRT according to individual programs at each stage with the aim of restoring motor activity and working capacity.

5. Prevention and Dispensary Observation

• To personalize the dose of basic therapy drugs for osteonecrosis (ATC calcium preparations, group A12AA, or #Osteogenon in combination with #cholecalciferol** 10–20 mcg per day or alfacalcidol** 0.5–1.0 mcg per day, or calcium carbonate + cholecalciferol or alfacalcidol + calcium carbonate [combination drugs]) it is recommended to monitor: blood total calcium levels throughout the entire treatment period under the supervision of an orthopedic trauma surgeon [54,55,222].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

• To monitor bone tissue restoration in the focus of osteonecrosis, regardless of its location, in all patients it is recommended to perform radiography of the affected part of the skeletal system at least once every 6 months, and joint MRI (single joint) at least once every 3–6 months [268].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

• Upon achieving bone tissue restoration in the focus of osteonecrosis, regardless of its location, in the presence of concomitant osteoporosis in all patients, it is recommended to continue osteoporosis treatment in accordance with current clinical guidelines for the diagnosis and treatment of osteoporosis or to refer the patient for follow-up by a geriatrician, general practitioner, or another specialist managing osteoporosis [58,221-223,261].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

6. Organization of Medical Care

Treatment of avascular necrosis is carried out on an outpatient basis, except in cases where there are indications for hospitalization (including medical transportation depending on the patient's condition).

Indications for hospitalization in a medical organization

The need for surgical treatment (core decompression (revascularizing osteoperforation), bone reconstruction, tibial osteotomy, femoral osteotomy, bone grafting (osteoplasty) of various skeletal bones, arthroplasty of various joints).

Indications for patient discharge from a medical organization

1. Surgery performed.

2. Patient mobilization within the ward.

3. No postoperative complications.

7. Additional Information

Late diagnosis of the disease and, consequently, delayed initiation of treatment worsen the prognosis. The natural course of osteonecrosis is directly related to the size and localization of the lesion. Small lesions (less than 15% of the femoral head) can completely resolve with treatment. Conversely, lesions involving more than 50% of the femoral head are highly likely to progress to collapse and ultimately require total joint arthroplasty.

A particularly significant impact is exerted by the patient's non-compliance with the orthopedic regimen, concomitant pathology, and chronic diseases. For instance, in patients with concomitant osteoporosis, treatment takes longer, which must be considered when determining management tactics. The baseline risk of cardiovascular or gastrointestinal pathology in patients with avascular necrosis must be taken into account when selecting medications.

Criteria for Evaluating the Quality of Medical Care

Stage of bone osteonecrosis detection

Stage of bone tissue repair monitoring

Stage of completion of osteonecrosis treatment

References

Appendix A1. Working Group Composition

Rodionova S.S., MD, Professor, Moscow, Member of the Association of Traumatologists and Orthopedists (ATOR), MAPO.

Torgashin A.N., PhD in Medical Sciences, Moscow, Member of ATOR, MAPO.

Akhtyamov I.F., MD, Kazan, Member of ATOR, MAPO.

Baikova A.R., Moscow, Trauma and Orthopedic Surgeon.

Geroeva I.B., MD, Professor, Honored Doctor of the Russian Federation, Member of the Union of Rehabilitologists of Russia.

Kovalenko A.N., Candidate of Medical Sciences, Member ofATOR.

Makarov M.A., Candidate of Medical Sciences. Moscow, Member of ARO.

Malanin D.A., Doctor of Medical Sciences. Volgograd, Member of ATOR.

Morozov A.K., Doctor of Medical Sciences. Moscow, Member of ATOR.

Mursalov T.K., Candidate of Medical Sciences. Moscow, Member of ATOR.

Nazarenko A.G., Doctor of Medical Sciences, Corresponding Member of the RAS, Moscow, Member of ATOR.

Ochkurenko A.A., Doctor of Medical Sciences, Professor, Moscow, Member of ATOR.

Otdelyonov V.A., Candidate of Medical Sciences, Moscow, Clinical Pharmacologist.

Smitienko I.O., Candidate of Medical Sciences. Moscow, Member of ARR.

Torgashina A.V., Candidate of Medical Sciences. Moscow, Member of ARR.

Shumsky A.A., Candidate of Medical Sciences. Moscow, Member of ATOR.

Conflict of interest: the authors declare no conflict of interest regarding the development of these clinical guidelines.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Trauma and orthopedic surgeons;

2. Rheumatologists;

3. Radiologists;

4. General practitioners (family physicians);

5. Physicians of other specialties involved in the diagnosis and treatment of joint pathologies.

Stages of evaluating the levels of evidence and grades of recommendation:

1. Definition of search and selection criteria for publications on clinical trials (CT) regarding the efficacy and/or safety of the medical intervention described in the recommendation statement.

2. Systematic search and selection of CT publications in accordance with the previously defined criteria.

Systematic search and selection of publications on clinical trials:

The evidence base for the recommendations consisted of publications retrieved via information retrieval in the following databases: Central Scientific Medical Library (CSML) "Russian Medicine", MEDLINE (US NLM), and COCHRANE Library; scientific electronic libraries eLibrary.ru and "CyberLeninka"; as well as on the Internet using Yandex, Google, and Google Scholar search engines, by reviewing leading specialized peer-reviewed domestic medical journals on the subject and treatment guidelines for fractures from the international Association for Osteosynthesis AO/ASIF.

The level of reliability of evidence contained in the publications was assessed in accordance with Tables 1 and 2. Publications with the highest level of evidence reliability were selected.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Table 1. Features of MRI findings at different stages of osteonecrosis

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

What is avascular bone necrosis (osteonecrosis)?

Avascular necrosis (osteonecrosis) is a severe polyetiological disease associated with the death of bone cells and the destruction of bone tissue, most commonly in the subchondral zone (close to the joint), rapidly leading to the development of arthrosis/arthritis in the affected joint.

Primary (spontaneous, idiopathic) osteonecrosis, the cause of which is often unknown, and secondary osteonecrosis, developing against the background of glucocorticoid use, alcohol abuse, radiation or chemotherapy, autoimmune diseases, and various coagulopathies, are distinguished.

The most common localizations of the disease are the femoral head (hip joint) or the femoral and tibial condyles (knee joint). The talus, humeral head, etc., may also be affected.

Two main mechanisms of osteonecrosis development are distinguished:

• Local impairment of blood supply as a result of trauma or microvascular thrombosis leads to the death of bone cells, increased bone resorption (destruction), and the development of arthrosis/arthritis in the affected joint. This mechanism is most characteristic of secondary osteonecrosis.

• In primary osteonecrosis (when the cause is unknown), the triggering mechanism is more often a disturbance of bone tissue metabolism, with bone destruction predominating over bone formation. This leads to microfractures of bone trabeculae, followed by impaired venous outflow, increased intraosseous pressure, increased hypoxia, bone cell death, and subchondral bone collapse.

As can be seen, in both cases, bone tissue destruction occurs with the subsequent development of arthrosis/arthritis. Timely diagnosis and pharmacotherapy, taking into account bone metabolism disorders, can halt the progression of the disease and preserve joint function.

Femoral head osteonecrosis is most frequently detected at the age of 33–45 years, with a male-to-female ratio of 3:1. As a rule, there is no history of prior joint trauma. One of the common causes may be alcohol abuse. Individuals with systemic diseases such as systemic lupus erythematosus, rheumatoid arthritis, sickle cell anemia, as well as those taking glucocorticoids or undergoing radiation or chemotherapy, are also at risk. However, in about 40% of patients, the cause of osteonecrosis remains unknown.

Osteonecrosis of the femoral and tibial condyles is more typical for women over 50 years of age. It usually occurs without trauma, although many patients note increased load in the days preceding the onset of the disease. One of the risk factors for osteonecrosis of the femoral and tibial condyles is a general loss of bone mineral density and the presence of systemic osteoporosis.

Osteonecrosis of the talus in the majority of patients develops after a sustained ankle injury, often if proper ankle immobilization was not performed post-injury.

How to suspect osteonecrosis?

Early diagnosis of the disease increases the chances of successful conservative therapy.

Early stages are considered to be lesions prior to the occurrence of subchondral bone collapse (destruction of the bone near the joint) and deformation of the articular surface.

Pain syndrome in the joint may occur without an apparent cause, sometimes following increased physical load a few days prior to the onset of pain.

If the pain syndrome does not resolve within 5–7 days despite taking NSAIDs, further evaluation is required.

If radiographic changes do not correspond to the severity of the pain syndrome, further evaluation is required.

If the patient regularly takes glucocorticoids or has a systemic disease and joint pain occurs, avascular necrosis must be ruled out.

Diagnostic methods

X-ray diagnostics is the most accessible method, but it has a significant drawback in diagnosing osteonecrosis: bone tissue changes on radiographs appear only at stage 2 of the disease. However, radiography allows for the detection of gross bone changes and differential diagnosis with a number of other conditions that may also be asymptomatic.

Magnetic resonance imaging (MRI) is the primary method for detecting early stages of avascular bone necrosis. It allows for the diagnosis of the disease at the very earliest stages, which manifest as bone tissue edema.

Dual-energy X-ray absorptiometry (DEXA) is an examination that measures bone mass based on mineral content (mainly calcium) in bone tissue and assesses overall bone loss.

Features of osteonecrosis therapy

Treatment tactics for osteonecrosis are determined individually by an orthopedic traumatologist depending on the localization and stage of the disease. In any case, the following types of therapy are distinguished: conservative (without surgery, but with immobilization of the affected limb), surgical (e.g., osteoperforation or osteotomy), and pharmacological (prescription of drugs for osteonecrosis treatment). Treatment of avascular necrosis is always combined: surgical or conservative, including osteonecrosis pharmacotherapy.

In avascular necrosis of the femoral head

According to indications (determined by an orthopedic traumatologist), the following are performed:

- conservative treatment;

- crutch-walking for at least three months;

- surgical treatment – osteoperforation (core decompression) of the osteonecrosis focus is performed, or, according to indications, other types of surgeries are performed, including arthroplasty.

CAUTION.

Following hip surgery, flexion in the hip joint beyond 90 degrees must be avoided.

You must not lift your knee higher than your hip joint (even when sitting), cross your legs, or spread them too far apart; falls must be avoided.

In most cases, following hip replacement surgery, crutch-walking with moderate weight-bearing on the operated limb is performed for the first two months, followed by walking with a cane in the opposite hand for up to six months.

Recovery after surgery depends not only on how well you follow the doctor's recommendations, but also on your overall health status. Therapeutic exercise improves blood circulation, helps restore joint functions, and prevents contractures.

General recommendations for medical treatment of osteonecrosis

Any drug therapy must be prescribed and monitored by a physician, as it is necessary to select the optimal, most effective and safe regimen, doses, and administration schedule. Uncontrolled intake of medications can, on the one hand, cause severe complications, and on the other hand, be completely ineffective.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1 ARCO Classification

Russian title: ARCO Classification.

Original title (if available): Classification ARCO (Association Research Circulation Osseous).

Source (official developer website, validation publication):

www.arco-intl.org

Type (underline):

- assessment scale

- score

- questionnaire

- other (specify):

Purpose: assessment of the stage and extent of the lesion.

Assessment tool, content: Radiography, MRI, CT.

Key (interpretation):

Appendix G2. Visual Analog Scale (VAS) for pain

Russian title: Visual Analogue Scale for pain.

Original title: Visual analogue scale (VAS).

Source: (official developer website, validation publication): Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011; 63 Suppl 11: S 240–252

Type: rating scale.

Purpose: pain assessment.

Content:

Key (interpretation): The VAS is a straight line 10 cm in length. The patient is asked to make a mark on the line corresponding to the intensity of the pain they are experiencing. The left border of the line corresponds to the definition "no pain", and the right border to "worst pain imaginable". The distance between the left end of the line and the made mark is measured in millimeters and recorded in the observation sheet.

Notes: It is recommended to perform the assessment when enrolling the patient in the study prior to any intervention (treatment, surgery). Since completing the VAS questionnaire does not take much time, the assessment can be performed daily throughout the course of treatment. Data obtained in this way can provide a valuable reflection of the analgesic effect of the treatment administered. In dynamic assessment, a change in pain intensity is considered objective and significant if the current VAS value differs from the previous one by more than 13 mm.

Typically, a paper, cardboard, or plastic ruler 10 cm in length is used. On the reverse side of the ruler, centimeter graduations are marked, allowing the physician (or nursing staff in foreign clinics) to record the obtained value and enter it into the observation sheet. The undeniable advantages of this scale are its simplicity and convenience.